Srinivasan Kavitha

Family History Is a Strong Risk Factor for Prevalent Angle Closure in a South Indian Population

PURPOSE To compare the prevalence of angle closure among siblings of patients with open angles (OAs), suspect angle closure (PACS), and either primary angle closure (PAC) or PAC glaucoma (PACG). DESIGN Cross-sectional, clinical study. PARTICIPANTS A total of 303 South Indian sibling pairs, including 81 OA probands, 143 PACS probands, and 79 PAC/PACG probands. METHODS Probands and siblings underwent a clinical examination, including gonioscopy by a masked grader, applanation tonometry, slit-lamp biomicroscopy, optic nerve evaluation, and A-scan ultrasonography. Probands and siblings were classified into 1 of 3 groups based on the phenotype of the more severely affected eye: OA, PACS, or PAC/PACG. Multivariable regression models were used to estimate the odds of prevalent angle closure in PACS or PAC/PACG siblings compared with OA siblings. MAIN OUTCOME MEASURES Prevalence and relative prevalence of angle closure and PAC/PACG among OA, PACS, and PAC/PACG siblings. RESULTS Mean sibling age was 49.7 ± 8.7 years, and 56.6% of siblings were females. Angle closure was more prevalent in both PACS siblings (35.0%) and PAC/PACG siblings (36.7%) compared with OA siblings (3.7%; P < 0.001). There was PAC/PACG present in 11.4% of PAC/PACG siblings compared with 4.9% of PACS siblings (P = 0.07) and 0% of OA siblings (P = 0.002). In multivariable models adjusting for sibling age and sex, the odds of angle closure was 13.6 times greater in angle closure (PACS or PAC/PACG) siblings compared with OA siblings (95% confidence interval [CI], 4.1-45.0; P < 0.001). Sibling angle-closure risk was also greater in female (odds ratio [OR], 2.3; 95% CI, 1.3-4.0; P = 0.005) and older siblings (OR, 1.5 per 10-year increment; 95% CI, 1.1-2.0; P = 0.02). Siblings of PAC/PACG probands had a 2.3-fold greater odds (95% CI, 0.8-6.5) of having PAC/PACG compared with siblings of PACS probands, although the association was not significant (P = 0.13). CONCLUSIONS In the South Indian population screened, siblings of angle-closure patients had a >1 in 3 risk of prevalent angle closure, whereas siblings of PAC/PACG patients had a >10% risk of prevalent PAC/PACG. Screening siblings of angle-closure patients is likely to be of high yield in finding undetected angle closure.

Association Study in a South Indian Population Supports rs1015213 as a Risk Factor for Primary Angle Closure

PURPOSE Three loci defined by single nucleotide polymorphisms (SNPs) rs11024102 in PLEKHA7, rs3753841 in COL11A1, and rs1015213 between the PCMTD1 and ST18 genes, recently have been associated with primary angle closure glaucoma (PACG). We explored the genetic association of these SNPs with subtypes of primary angle closure in a South Indian population. METHODS The study included three case definitions: primary angle closure/primary angle closure glaucoma (PAC/PACG, N = 180); primary angle closure suspect (PACS, N = 171), and a combined any-angle closure group. Controls consisted of 411 individuals from South India. Genotyping for all three SNPs was performed using the TaqMan allelic discrimination assay. Genetic association was estimated using a χ(2) test statistics and logistic regression. RESULTS Among the three studied SNPs, significant genetic association was identified for rs1015213 in the PAC/PACG (P = 0.002) and any-angle closure (P = 0.003) analyses. However, no significant genetic association was seen when in PACS subjects (P = 0.052). SNPs rs3753841 and rs11024102 showed no evidence of genetic association with angle-closure phenotypes (P > 0.05) in South Indian participants. CONCLUSIONS In our study, rs1015213 (located in the intergenic region between PCMTD1 and ST18) was associated significantly with PAC/PACG, confirming prior reports of an association between this region and angle closure glaucoma. Further work with a larger sample size is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.

Angle Closure Phenotypes in Siblings of Patients at Different Stages of Angle Closure

Financial Disclosures: The authors made the following disclosures: M.Y.K.: Consultant e Alcon, Allergan, Aerie Pharmaceuticals, Forsight Vision 5, and Tempest Ocular; Other e Alcon, Allergan, Aerie Pharmaceuticals, Forsight Vision 5, Tempest Ocular; Grants e Alcon, Allergan, Clarvista Medical, New World Medical, AMO, Glaukos, Aerie Pharmaceuticals, outside the submitted work; Patent e Clarvista, Glaukos, AMO, Shapetech; Grant funding NEI. P.Y.R.: Grants e National Eye Institute, Research to Prevent Blindness, outside the submitted work. L.K.S.: Other e Allergan, Sensimed, New World Medical; Grants e Alcon, outside the submitted work. J.R.S.: Grants e Alcon, Allergan, Bausch & Lomb, Glaukos, Regeneron, outside the submitted work. Supported by the Slater Family Endowment (M.Y.K.). The sponsor or funding organization had no role in the design or conduct of this research.

Genetic Complexity of Primary Angle-Closure Glaucoma in Asians

Glaucoma is a group of optic neuropathies, characterized by progressive loss of axons in the optic nerve and degeneration of retinal ganglion cells accompanied by visual field loss. It is the second foremost irreversible cause of blindness after cataract worldwide. Even though primary open-angle glaucoma (POAG) is a more prevalent form of glaucoma, primary angle-closure glaucoma (PACG) accounts for substantial cause of visual morbidity worldwide. PACG is one of the subtypes of glaucoma with multifactorial aetiology characterized by the opposition of the iris to the trabecular meshwork, thus hindering aqueous outflow from the angle of an eye. It is more common among the people of Asian descent than Europeans. It is a heterogeneous disorder with complex genetic basis affecting many individuals within a family. Since, it is often asymptomatic in early stages and its late onset nature, diagnosis is frequently delayed. Therefore, understanding the genetic aspects and identification of risk factors will shed light to unravel the complexity of this complex disorder. Several genetic approaches and molecular biology techniques can be used to comprehend and identify susceptibility loci for angle-closure glaucoma. This chapter gives insights into the current status concerning epidemiology, risk factors, disease classification, its mechanism and genetics of angle-closure glaucoma.